ThisAREA application has the following major goals: (1) To developan inexpensive, rapid and inexcessible animal model, for screening human nuclear autoantibodies in functional terms. It is proposed to use chicken liver nuclei, isolated from animals before, during and afterestrogenicinduction of yolk protein synthesis, and ask whether the antigens of such autoantibodies are inducible bythis well-defined hormonal trigger. (2) To establish quantitative parameters in the above system, whereby autoantibodies can be assayed by immunoflourescence microscopy of isolated nuclei and by immunoblotting to PAGE-separated nuclear proteins. (3) To involve both undergraduate and MS-level students in laboratory research using modern technology and projects of clear biomedical importance. While most autoantibodies from patients with autoimmune disorders have not been linked directly with disease pathogenesis, many are directed against universally important nuclear antigens. Consequently, assays based on a chicken tissue which can be fully reprogrammed by a single exposure to estrogen, seem appropriate. An advantage of this approach is that nuclei can prepared in bulk from controls and experimental animals at various times post hormone, and then stored at -80 degrees celsius for extended use and for multiple in vitro assays of antibodies, singly and in combination. A broad panel of autoantibodies and monoclonal antibodies is available for testing, thanks to collaborative support from the Autoimmune Disease Center at Scripps Clinic, La Jolla, California. The investigators will look for induction and co-localization in nuclei, of individual antigens and the ES-receptor (using MAB H-222, Abbott Labs) after estrogenic stimulation, particularly in terms of RNP components, nuclear bodies and other structures involved in transcription, RNA processing and export.In the long term, these studies will be followed up by immunocytochemistry at the E.M. level.